chr20-32209825-T-C

Position:

• chr20-32209825-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015352.2(POFUT1):​c.125-246T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,012 control chromosomes in the GnomAD database, including 10,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (10041 hom., cov: 32)
• Consequence: POFUT1 NM_015352.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.882

Genes affected

POFUT1 (HGNC:14988): (protein O-fucosyltransferase 1) This gene encodes a member of the glycosyltransferase O-Fuc family. This enzyme adds O-fucose through an O-glycosidic linkage to conserved serine or threonine residues in the epidermal growth factor-like repeats of a number of cell surface and secreted proteins. O-fucose glycans are involved in ligand-induced receptor signaling. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-32209825-T-C is Benign according to our data. Variant chr20-32209825-T-C is described in ClinVar as [Benign]. Clinvar id is 1225293.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POFUT1	NM_015352.2	c.125-246T>C		intron_variant		ENST00000375749.8	NP_056167.1
POFUT1	NM_172236.2	c.125-246T>C		intron_variant			NP_758436.1
POFUT1	XM_047440079.1	c.-79+1760T>C		intron_variant			XP_047296035.1
POFUT1	XR_007067447.1	n.187-246T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POFUT1	ENST00000375749.8	c.125-246T>C		intron_variant		1	NM_015352.2	ENSP00000364902	P1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45084 AN: 151894 Hom.: 10011 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.0821

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.264

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 45177 AN: 152012 Hom.: 10041 Cov.: 32 AF XY: 0.292 AC XY: 21729 AN XY: 74320

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.0819

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.262

Alfa AF: 0.215 Hom.: 1851

Bravo AF: 0.325

Asia WGS AF: 0.246 AC: 855 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.60
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11905172; hg19: chr20-30797628;